Dr.

Huda Adnan
C.A.B.O.G

INTRODUCTION
More than (50%) of the women consume drugs
(other than tonics) during pregnancy (the
average is 3 to 4 drugs during the 9 months
period ) in addition to non pharmacological
substances that contain drugs which are
potentially dangerous to the fetus such as
cigarettes. Most drugs are safe to use in
pregnancy ,however some harmful effects had
been described to the fetus or to the neonate.

1
 Prescribing drugs during pregnancy
must be considered in 2 points:
1st : the physiological changes
during pregnancy may alter the
therapeutic agent (e.g . by affecting
absorption).
2nd :the therapeutic agent may affect
the fetus or neonate.

Maternal pharmacokinetics:
1.Drugs absorption: during pregnancy the
gastrointestinal transit is prolonged due to slow
emptying of the stomach & reduce gastric &
intestinal motility.
2.Drugs distribution: lipid solubility & protein
binding affect drugs distribution ( drugs which is
low lipid solubility & highly bound to plasma protein
result in low free drugs to be transferred to the
fetus). There is also an increase in total body
water & plasma volume therefore there will be
more dilutional effects on the drugs . plasma
albumin is also decreased.

2
 3.Drugs metabolism: water soluble drugs
are eliminated unchanged, while lipid
soluble drugs are metabolized by
oxidation, conjugation in placenta & fetal
liver before being excreted in bile or
urine.
4.Drugs excretion : renal blood flow
increases as well as GFR & creatinin
clearance, so water soluble drugs are
excreted rapidly.

Fetal pharmacokinetics:
Almost all drugs with systemic effect on the fetus
( except heparin & insulin with molecular Wt,
more than 1000 unit ) cross the placenta to reach
the fetus by simple diffusion that depends on its
plasma conc, degree of ionization & lipid
solubility . the drugs distributes into the placenta ,
fetal liver & fetal adrenal glands . the fetus has
limited ability to metabolite drugs in the liver &
inefficient blood brain barrier.

3
 Effect of the drugs on the fetus:
The effects range from killing the embryo to no
effects. Drugs or their metabolites can cause
adverse fetal effects.
The harmful fetal effects depend on:
1-the amount of the drug that enters fetal
circulation.
2-dosage & rout of administration.
3-duration of use .
4-physical condition of the mother & the fetus.
5-maturity of the fetus.

6-time of gestational age during which the drug has

been use.
7-concurrent use of other agents.
8-fetal metabolism.
Timing of embryo & fetal development:
Pre embryonic period: (0-2 weeks) during the 1st two
weeks after ovulation the embryo is thought to be
resistant to any teratogenic effects of medicines.
Embryonic period: (2 weeks - 8 weeks ) it’s the most
critical period as it’s a period of organogenesis ,
exposure during this period may cause birth defect &
congenital malformation.

4
 Fetal period: ( after 8th weeks – delivery) exposure
in this period may affect growth & functional
development.

The harmful effect includes :

1. Mutagen : causes a change in a gene structure
leading to miscarriage , congenital abnormalities,
mental retardation. E.g radiation.
2.Carcinogen : induces or promotes cancer , e.g
stillbisteroll.
3.teratogen: interferes with fetal development after
conception leading to permanent alteration in the
structure & function in the offspring (like limb
deformities , deafness , cardiac defect , growth
retardation ).

These include hormones (androgen)

,anticancer (methotrexate)
,anticonvulsant (phenytoin, sodium
valproate) , oral anticoagulant
(warfarin) & antithyroid(thiouracil
&carbimazole) &radioactive iodide.
The FDA classifies drugs in one of 5
categories based on their teratogenic
potential :

5
 Category A
 No risk
 Controlled studies in pregnant women shows no risk.
Category B
 No risk in human
 Controlled animal studies have not shown fetal risk
but no studies in human .
Category C
 Risk not ruled out
 Controlled animal studies have shown adverse fetal
effect & there are no human studies or there are no
Controlled studies in human or animals.

Category D
 Positive evidence of risk
 Controlled studies in human show
adverse fetal effect but the benefit are
greater than the risk
Category x
 Contra indicated
 Controlled studies in animal & human
show adverse fetal effect but the risk
are greater than benefit

6
  Examples of common drugs in pregnancy:
Analgesia :
 Aspirin: its safe in low dose SE:
oligohydrominous , premature closure of
ductus arteriosus , pulmonary hypertension &
peripartum bleeding.
 *paracetomol: is the analgesic of choice in
pregnancy .
 *other NSAIDs that commonly used are
indomethacin, Ibuprofen,&naproxen. SE: like
aspirin but in large doses may cause fetal
renal failure .

 Narcotic: safe but cause addiction, neonatal

withdrawal &respiratory depression.
Anticoagulant :
 *heparin: safe in pregnancy ,large molecular Wt
does not cross the placenta .
 UFH: SE: osteoporosis, thrombocytopenia,
sterile abscess.
 LMWH: once daily dose so less SE .
 *warfarin: cause warfarin embryopathy(nasal
hypoplasia, stippled bone epiphyses,
microcephaly, IUGR, mental retardation .

7
 Antihypertensive :
 *methyldopa: (aldomate): safe SE: GIT upset,
headache, dizziness, & postural hypertension.
 *hydralazine :safe SE: GIT upset, tachycardia,
palpitation, & fluid retention.
 *B.blocker: safe SE: IUGR, mask fetal
response to hypoxia, &neonatal hypoglycemia.
 *ACEI: contraindicated causing renal
anomalies, pulmonary hypoplasia,
oligohydrominous & skull defect.

diuretics: usually not used in pregnancy

because it reduce blood volume.
Thyroid drugs:
 Propylthouracil: cross the placenta lead to
fetal goiter,hepatotoxic.
 *methimazole: associated with cutis aplasia,
, esophageal atrasia, agranulocytosis.
 *thyroid drugs: poorly cross the placenta so
safe.
 *radioactive iodine: contraindicated.

8
 Psychotropic drugs:
 *lithium: causing cardiac defect especially Ebstain's
anomalies
 *TAD : imipramine may cause heart defect &
withdrawal symptoms & amitriptyline not cause birth
defect.
 *SSRI: fluoxetine may cause withdrawal symptoms in
the neonate, pulmonary hypertension, & cardiac
defect.
 *diazepam: no birth defect but in late pregnancy may
induce transient hypotonia, hypothermia, & respiratory
depression.
 *phenothiazine & chlorpromazine no birth defect but
in late pregnancy induce extra pyramidal effects.

Anti convulsants :
 *carbamazepine: cause malformation like
hydantoin groups & induce neural tubes
defect.
 *phenytoin: cause cleft palate & lip, broad
nasal bridge, cardiac defect ,IUGR,&
mental retardation.
 *Na valproate: cause neural tubes defect
 *lamotrigine & gabapentin : are less
teratogenic.

9
 Antibiotics :
 Ampicillin: safe but augmentin advisable to
avoid because has adverse fetal effect
(necrotizing enterocolitis) but no birth defect.
 *erythromycin succinate: safe but ineffective for
treatment of fetus.
 *cephalosporin :safe
 *aminoglycosides :teratogenic cause ototoxicity
& nephrotoxicity.
 tetracycline :cause teeth discolouration & bone
chelation

 sulfonamide : safe but not used in T3

due to neonatal hyperbilirubinemia.
 *trimethoprim :avoided due to neural
tube defect & cardiac defect.
 *chlormphenicol: avoided grey baby
syndrome.

10
 *nitrofurantoin: safe
 *ciprofloxacin: bone & cartilage defect &
arthropathy.
 *metronidazole: safe in early & late
pregnancy.
 Steroid :cleft palate.
 Cytotic drugs : not safe.
 Retinoids: not safe
 Danazole : virilization of femle fetus.
 DES: clear cell carcinoma & congenital
anomalies of uterus

11